15-74820742-A-G

Variant names:

• chr15-74820742-A-G
• rs1531163
• NM_021819.3:c.882A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021819.3(LMAN1L):​c.882A>G​(p.Lys294Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 1,613,098 control chromosomes in the GnomAD database, including 14,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (3586 hom., cov: 32)
  • Exomes 𝑓: 0.075 (10631 hom.)
• Consequence: LMAN1L NM_021819.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 14 publications found

Genes affected

LMAN1L (HGNC:6632): (lectin, mannose binding 1 like) This gene encodes a mannose-binding type 1 transmembrane protein that contains an N-terminal lectin-like carbohydrate recognition domain. The encoded protein is similar in structure to lectins found in leguminous plants. This lectin is thought to transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. [provided by RefSeq, Jan 2017]

ENSG00000261606 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN1L	NM_021819.3	c.882A>G	p.Lys294Lys	synonymous_variant	Exon 8 of 14	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10	c.882A>G	p.Lys294Lys	synonymous_variant	Exon 8 of 14	1	NM_021819.3	ENSP00000310431.5
LMAN1L	ENST00000379709.7	c.846A>G	p.Lys282Lys	synonymous_variant	Exon 7 of 13	1		ENSP00000369031.3
ENSG00000261606	ENST00000488000.6	n.1412A>G		non_coding_transcript_exon_variant	Exon 6 of 14	2
LMAN1L	ENST00000565585.5	n.1276A>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24092 AN: 151912 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.132 AC: 33083 AN: 250460 AF XY: 0.134

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.0735

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0994

GnomAD4 exome AF: 0.0752 AC: 109907 AN: 1461068 Hom.: 10631 Cov.: 32 AF XY: 0.0814 AC XY: 59186 AN XY: 726782

African (AFR) AF: 0.387 AC: 12949 AN: 33474

American (AMR) AF: 0.174 AC: 7751 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 1718 AN: 26082

East Asian (EAS) AF: 0.186 AC: 7384 AN: 39694

South Asian (SAS) AF: 0.330 AC: 28494 AN: 86222

European-Finnish (FIN) AF: 0.0689 AC: 3652 AN: 52980

Middle Eastern (MID) AF: 0.101 AC: 581 AN: 5762

European-Non Finnish (NFE) AF: 0.0371 AC: 41209 AN: 1111810

Other (OTH) AF: 0.102 AC: 6169 AN: 60374

GnomAD4 genome AF: 0.159 AC: 24155 AN: 152030 Hom.: 3586 Cov.: 32 AF XY: 0.164 AC XY: 12154 AN XY: 74334

African (AFR) AF: 0.372 AC: 15432 AN: 41446

American (AMR) AF: 0.132 AC: 2017 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3468

East Asian (EAS) AF: 0.181 AC: 932 AN: 5142

South Asian (SAS) AF: 0.359 AC: 1730 AN: 4822

European-Finnish (FIN) AF: 0.0791 AC: 838 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0382 AC: 2597 AN: 67968

Other (OTH) AF: 0.135 AC: 285 AN: 2106

Alfa AF: 0.0838 Hom.: 1108

Bravo AF: 0.167

Asia WGS AF: 0.339 AC: 1175 AN: 3478

EpiCase AF: 0.0368

EpiControl AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		0.074
PromoterAI		0.00060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1531163; hg19: chr15-75113083; COSMIC: COSV59001100; COSMIC: COSV59001100;